Benzo[a]pyrene-induced nitric oxide production acts as a survival signal targeting mitochondrial membrane potential

Hardonnière, Kévin; Huc, Laurence; Podechard, Normand; Fernier, Morgane; Tekpli, Xavier; Gallais, Isabelle; Sergent, Odile; Lagadic‐Gossmann, Dominique

doi:10.1016/j.tiv.2015.06.010

Cited by 16 publications

(22 citation statements)

References 47 publications

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“…In order to test whether the B[a]P-increased mitochondrial IF1 protein level was involved in both the glycolytic shift and cell survival signaling we recently reported 21, 22 , we decided to test the role of IF1 towards both glycolytic shift and cell death by using a siRNA approach. First, western blotting experiments were carried out in order to validate the siRNA targeting IF1 (siIF1) used.…”

Section: Resultsmentioning

confidence: 99%

“…S2C). Our previous work indicated that B[a]P metabolism by CYP1B1 could play a role in metabolism reprogramming 21, 22 . However, as for CH223191, α-naphthoflavone did not prevent IF1 increase.…”

Section: Discussionmentioning

confidence: 99%

“…The F258 rat liver epithelial cell line was cultured in Williams’ E medium supplemented with 10% fetal calf serum, 2 mM L-glutamine, at 37 °C under a 5% CO 2 atmosphere and treated 24 h following seeding as previously described 21, 28 . F258 cells were treated with B[a]P for 24, 48 and 72 h. Cells were seeded at a density of 2.5× 10 3 cells/cm 2 one day before treatment, and the medium changed before exposures.…”

Section: Methodsmentioning

confidence: 99%

“…Cell toxicity was measured by analysis of chromatin condensation and fragmentation in the cell nucleus as previously described 21 .…”

Section: Methodsmentioning

confidence: 99%

“…These widespread contaminants are notably found in cigarette smoke, exhaust fumes, grilled meat, among others, and have been related to tumor development, notably in lung and liver 18, 19 . We recently demonstrated that a low concentration of benzo[a]pyrene (B[a]P), the prototype molecule of PAHs which is classified as human carcinogen of group 1 by IARC 20 , not only hyperpolarized mitochondria 21 , but also induced both a mitochondrial matrix acidification, a glycolytic shift, and an EMT/migration phenotype of liver cells 22 . Furthermore, a reverse activity of complex V upon B[a]P exposure, was also previously suggested 23 .…”

Section: Introductionmentioning

confidence: 99%

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Role for the ATPase inhibitory factor 1 in the environmental carcinogen-induced Warburg phenotype

Hardonnière¹,

Fernier²,

Gallais³

et al. 2017

Sci Rep

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Most tumors undergo metabolic reprogramming towards glycolysis, the so-called Warburg effect, to support growth and survival. Overexpression of IF1, the physiological inhibitor of the F0F1ATPase, has been related to this phenomenon and appears to be a relevant marker in cancer. Environmental contributions to cancer development are now widely accepted but little is known about the underlying intracellular mechanisms. Among the environmental pollutants humans are commonly exposed to, benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons (PAHs), is a well-known human carcinogen. Besides apoptotic signals, B[a]P can also induce survival signals in liver cells, both likely involved in cancer promotion. Our previous works showed that B[a]P elicited a Warburg-like effect, thus favoring cell survival. The present study aimed at further elucidating the molecular mechanisms involved in the B[a]P-induced metabolic reprogramming, by testing the possible involvement of IF1. We presently demonstrate, both in vitro and in vivo, that PAHs, especially B[a]P, strongly increase IF1 expression. Such an increase, which might rely on β2-adrenergic receptor activation, notably participates to the B[a]P-induced glycolytic shift and cell survival in liver cells. By identifying IF1 as a target of PAHs, this study provides new insights about how environmental factors may contribute to related carcinogenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Cell toxicity was measured by analysis of chromatin condensation and fragmentation in the cell nucleus as previously described 21 .…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role for the ATPase inhibitory factor 1 in the environmental carcinogen-induced Warburg phenotype

Hardonnière¹,

Fernier²,

Gallais³

et al. 2017

Sci Rep

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Genetic and Epigenetic Dysregulation in Environmental Disease

Ramos,

Hassanin,

Wang

2024

Comprehensive Precision Medicine

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Disturbances in H+ dynamics during environmental carcinogenesis

et al. 2019

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Abbreviations: B[a]P: benzo[a]pyrene; GPCR: G-protein coupled receptor; MCT: monocarboxylate transporter; NHE1: Na + /H + exchanger 1HIGHLIGHTS Benzo[a]pyrene, a well-known environmental carcinogen, alters H + dynamics. NHE1 activation by B[a]P plays a key role in H + dynamics alterations. B[a]P-altered pH controls cell death/survival balance via mitochondria and lysosome. ABSTRACTDespite the improvement of diagnostic methods and anticancer therapeutics, the human population is still facing an increasing incidence of several types of cancers. According to the World Health Organization, this growing trend would be partly linked to our environment, with around 20% of cancers stemming from exposure to environmental contaminants, notably chemicals like polycyclic aromatic hydrocarbons (PAHs). PAHs are widespread pollutants in our environment resulting from incomplete combustion or pyrolysis of organic material, and thus produced by both natural and anthropic sources; notably benzo[a]pyrene (B[a]P), i.e. the prototypical molecule of this family, that can be detected in cigarette smoke, diesel exhaust particles, occupational-related fumes, and grilled food. This molecule is a well-recognized carcinogen belonging to group 1 carcinogens. Indeed, it can target the different steps of the carcinogenic process and all cancer hallmarks. Interestingly, H + dynamics have been described as key parameters for the occurrence of several, if not all, of these hallmarks. However, information regarding the role of such parameters during environmental carcinogenesis is still very scarce. The present review will thus mainly give an overview of the impact of B[a]P on H + dynamics in liver cells, and will show how such alterations might impact different aspects related to the finely-tuned balance between cell death and survival processes, thereby likely favoring environmental carcinogenesis. In total, the main objective of this review is to encourage further research in this poorly explored field of environmental molecular toxicology.

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Benzo[a]pyrene-induced nitric oxide production acts as a survival signal targeting mitochondrial membrane potential

Cited by 16 publications

References 47 publications

Role for the ATPase inhibitory factor 1 in the environmental carcinogen-induced Warburg phenotype

Role for the ATPase inhibitory factor 1 in the environmental carcinogen-induced Warburg phenotype

Genetic and Epigenetic Dysregulation in Environmental Disease

Disturbances in H+ dynamics during environmental carcinogenesis

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